Trial Review

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12620000618954
Ethics application status
Approved
Date submitted
12/03/2020
Date registered
27/05/2020
Date last updated
27/03/2023
Date data sharing statement initially provided
27/05/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The GENTLER Trial: GenesisCare Epithelial Neoplasia Trial using Lighter dose Extensive field Radiotherapy
Scientific title
GenesisCare Epithelial Neoplasia Trial using Lighter dose Extensive field Radiotherapy
Secondary ID [1] 299645 0
None
Universal Trial Number (UTN)
U1111-1242-5619
Trial acronym
GENTLER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Skin cancer 316199 0
Condition category
Condition code
Cancer 314490 314490 0 0
Non melanoma skin cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Volumetric modulated arc therapy (VMAT) radiation: a total dose of 30 Gy will be delivered in 15 fractions as either

1) 2 Gy per fraction (10 Gy in 5 fractions), 5 days per week, treated alternate weeks over a period of 5 weeks OR

2) 2 Gy per fraction treated 3 times per week, over 5 weeks

The treatment schedule is determined by participant preference and/or investigator decision.
Intervention code [1] 316818 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 322818 0
To demonstrate the efficacy of low-dose VMAT radiotherapy for ESFC of the skin 12 months after completion of radiotherapy as defined by response rate. Treatment response is defined as greater than or equal to 75% clearance of the in-field in situ disease based on clinical assessment
Timepoint [1] 322818 0
12 months after the completion of radiotherapy
Secondary outcome [1] 379883 0
To determine the proportion of patients that require subsequent interventions within the treated field by documenting any recurrence on new lesion and treatment given.
Timepoint [1] 379883 0
12 months after the completion of radiotherapy
Secondary outcome [2] 379884 0
To determine the proportion of patients who develop invasive keratinocyte carcinoma in the treated field within 12 months of completing treatment. This is done by documenting either a recurrence or new lesion if this occurs.
Timepoint [2] 379884 0
12 months after the completion of radiotherapy
Secondary outcome [3] 379885 0
To evaluate the cosmetic appearance of treated skin areas 12 months after completion of radiotherapy as measured by the Lovett cosmesis score
Timepoint [3] 379885 0
12 months after the completion of radiotherapy
Secondary outcome [4] 379886 0
To assess acute and late toxicity rates up to 12 months after completion of radiotherapy by documenting any toxicities in the case report form.
(This is a composite secondary outcome)
Timepoint [4] 379886 0
12 months after completion of radiotherapy
Secondary outcome [5] 379887 0
To assess the proportion of patients that complete treatment by documenting completion in case report forms
Timepoint [5] 379887 0
Planned end of treatment date
Secondary outcome [6] 379888 0
To assess quality of life using patient reported outcomes DLQI and EQ-5D-5L
Timepoint [6] 379888 0
12 months after the completion of radiotherapy

Eligibility
Key inclusion criteria
1. Be aged 50 years or greater;

2. Have ESFC greater than 50 cm2;

3. Provide written informed consent; and

4. Fulfil at least two of the following three criteria (a, b, c):
a. Karnofsky performance score of less than or equal to 70;
b. Be unable to complete a fully fractionated, long-course of treatment due to a comorbidity or the requirement for nursing home care;
c. Be aged greater than or equal to 70 years

5. Charlson Comorbidity Score greater than or equal to 5

6. Willing to use adequate contraception measures (both in vivo and in vitro) during and for six months after radiation treatment for participants who will engage in the conception of a child
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Received local therapy within the last 4 weeks. This includes excision, cryotherapy, photo-dynamic therapy, radiotherapy or topical agents including 5FU, imiquimod ingenol mebutatte.

2. Have a clinically or biopsy-proven invasive skin malignancy within the treatment field to be treated which has either been untreated, or incompletely excised within the last 6 months

3. Currently receiving systemic chemotherapy or treatment with new targeted drugs (e.g. immunotherapy, tyrosine kinase inhibitors or BRAF inhibitors);

4. Are concurrently using radio sensitising drugs for medical comorbidities (e.g. methotrexate for rheumatoid arthritis, hydroxyurea etc);

5. For patients who are having lower limbs treated and have any of the following:
• Chronic lymphoedema with pitting oedema, peripheral vascular disease in the form of intermittent claudication or critical ischemia
• Chronic leg ulcer within the proposed treatment field
• Relapsing cellulitis

6. Have received prior radiotherapy to the same treatment site or

7. Any other medical condition as defined by the investigator which significantly impacts the patient’s involvement and suitability in this study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This is a non-randomised trial. Therefore, allocation concealment is not applicable.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary analysis will be conducted on an intention-to-treat basis, with all patients registered included in the analysis, irrespective of whether they received treatment according to the protocol. The full analysis set, on which all efficacy summaries will be based, will include all subjects registered. The safety population will include all patients who received at least one dose of radiation and this population will be used for all summaries of safety and toxicity.

The number of patients responding at 12 months (primary endpoint) will be reported together with the proportion (out of the total number of patients with non-missing response assessments) and 95% confidence interval, calculated using the Wilson score method. The actual % clearance for each subject will also be summarised. Missing data will not be imputed in the primary analysis. To assess the impact of the missing data on the results, sensitivity analyses will be performed for the primary endpoint, imputing data for missing assessment based on reasons for withdrawal from the study. Further detail will be provided in the Statistical Analysis Plan for this study.

For the secondary endpoints, the number and proportion of patients with response at end of treatment and 6 months, requiring subsequent interventions within 12 months, with in-field invasive disease within 12 months and completing treatment according to protocol will be summarised, using the Wilson score method for calculation of 95% confidence intervals for the proportions.

The number and proportion of patients with each category of Lovett cosmesis score (poor, fair, good, excellent) will be summarised. Total DLQI and EQ-5D-5L scores will be summarised (non-missing n, mean, SD, median, range) at baseline, 6 months and 12 months; the change from baseline to 6 months and 12 months will also be summarised.

Adverse events will be summarised descriptively.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
27/07/2020
Actual
21/07/2020
Date of last participant enrolment
Anticipated
16/03/2023
Actual
5/12/2022
Date of last data collection
Anticipated
15/03/2024
Actual
Sample size
Target
100
Accrual to date
Final
46
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 15834 0
St Andrew's Hospital Inc - Adelaide
Recruitment hospital [2] 15835 0
Tennyson Centre Day Hospital - Kurralta Park
Recruitment hospital [3] 15836 0
Genesis Cancer Care - Tugun - Tugun
Recruitment hospital [4] 15837 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [5] 15838 0
Mater Sydney - North Sydney
Recruitment hospital [6] 16701 0
GenesisCare – Shenton House - Joondalup
Recruitment hospital [7] 16702 0
GenesisCare – Wembley - Wembley
Recruitment hospital [8] 20993 0
Flinders Private Hospital - Bedford Park
Recruitment hospital [9] 20994 0
Calvary Central Districts Hospital - Elizabeth Vale
Recruitment hospital [10] 20995 0
Genesis Cancer Care - Wesley - Auchenflower
Recruitment hospital [11] 20996 0
Genesis Cancer Care - Chermside - Chermside
Recruitment postcode(s) [1] 29279 0
5000 - Adelaide
Recruitment postcode(s) [2] 29280 0
5037 - Kurralta Park
Recruitment postcode(s) [3] 29281 0
4224 - Tugun
Recruitment postcode(s) [4] 29282 0
3144 - Malvern
Recruitment postcode(s) [5] 29283 0
2060 - North Sydney
Recruitment postcode(s) [6] 30300 0
6027 - Joondalup
Recruitment postcode(s) [7] 30301 0
6014 - Wembley
Recruitment postcode(s) [8] 35824 0
5042 - Bedford Park
Recruitment postcode(s) [9] 35825 0
5112 - Elizabeth Vale
Recruitment postcode(s) [10] 35826 0
4066 - Auchenflower
Recruitment postcode(s) [11] 35827 0
4032 - Chermside

Funding & Sponsors
Funding source category [1] 304117 0
Commercial sector/Industry
Name [1] 304117 0
GenesisCare
Country [1] 304117 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
GenesisCare
Address
Buildings 1 & 11, The Mill
41-43 Bourke Road, Alexandria,
NSW 2015
Country
Australia
Secondary sponsor category [1] 304332 0
None
Name [1] 304332 0
Address [1] 304332 0
Country [1] 304332 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304604 0
Monash Health
Ethics committee address [1] 304604 0
Ethics committee country [1] 304604 0
Australia
Date submitted for ethics approval [1] 304604 0
22/01/2020
Approval date [1] 304604 0
12/06/2020
Ethics approval number [1] 304604 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97550 0
Dr Andrew Potter
Address 97550 0
GenesisCare,
St Andrew's Hospital,
352 South Terrace,
Adelaide, SA 5000
Country 97550 0
Australia
Phone 97550 0
+61 8 8228 6700
Fax 97550 0
Email 97550 0
[email protected]
Contact person for public queries
Name 97551 0
Andrew Potter
Address 97551 0
GenesisCare,
St Andrew's Hospital,
352 South Terrace,
Adelaide, SA 5000
Country 97551 0
Australia
Phone 97551 0
+61 8 8228 6700
Fax 97551 0
Email 97551 0
[email protected]
Contact person for scientific queries
Name 97552 0
Andrew Potter
Address 97552 0
GenesisCare,
St Andrew's Hospital,
352 South Terrace,
Adelaide, SA 5000
Country 97552 0
Australia
Phone 97552 0
+61 8 8228 6700
Fax 97552 0
Email 97552 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual line-by-line participant data will not be available. Only de-identified data will be published.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.